Exercise and spinal manipulative therapy are commonly used for the treatment of chronic low back pain (CLBP) in Australia. Reduction in pain intensity is a common outcome; however, it is only one measure of intervention efficacy in clinical practice. Therefore, we evaluated the effectiveness of two common clinical interventions on physical and self-report measures in CLBP. Participants were randomized to a 6-month intervention of general strength and conditioning (GSC; n = 20; up to 52 sessions) or motor control exercise plus manual therapy (MCMT; n = 20; up to 12 sessions). Pain intensity was measured at baseline and fortnightly throughout the intervention. Trunk extension and flexion endurance, leg muscle strength and endurance, paraspinal muscle volume, cardio-respiratory fitness and self-report measures of kinesiophobia, disability and quality of life were assessed at baseline and 3- and 6-month follow-up. Pain intensity differed favoring MCMT between-groups at week 14 and 16 of treatment (both, p = 0.003), but not at 6-month follow-up. Both GSC (mean change (95%CI): −10.7 (−18.7, −2.8) mm; p = 0.008) and MCMT (−19.2 (−28.1, −10.3) mm; p < 0.001) had within-group reductions in pain intensity at six months, but did not achieve clinically meaningful thresholds (20mm) within- or between-group. At 6-month follow-up, GSC increased trunk extension (mean difference (95% CI): 81.8 (34.8, 128.8) s; p = 0.004) and flexion endurance (51.5 (20.5, 82.6) s; p = 0.004), as well as leg muscle strength (24.7 (3.4, 46.0) kg; p = 0.001) and endurance (9.1 (1.7, 16.4) reps; p = 0.015) compared to MCMT. GSC reduced disability (−5.7 (−11.2, −0.2) pts; p = 0.041) and kinesiophobia (−6.6 (−9.9, −3.2) pts; p < 0.001) compared to MCMT at 6-month follow-up. Multifidus volume increased within-group for GSC (p = 0.003), but not MCMT or between-groups. No other between-group changes were observed at six months. Overall, GSC improved trunk endurance, leg muscle strength and endurance, self-report disability and kinesiophobia compared to MCMT at six months. These results show that GSC may provide a more diverse range of treatment effects compared to MCMT.